Fruquintinib plus sintilimab in patients with either treatment-naive or previously first line treated metastatic clear-cell renal cell carcinoma (ccRCC): Results from a multicenter, single-arm phase 2 study.
Authors: Dingwei Ye, Xin Yao, Zhisong He, Hong Luo, Guiling Li, Jianming Guo, Lei Diao, Hua Xu, Yu Fan, Yuan Li, Jiquan Fan, Xiaoyi Hu, Puhan Lu, Haiyan Shi, Panfeng Tan, Songhua Fan, Michael Shi, Weiguo Su
Journal: Journal of Clinical Oncology (2023)

e16514 Background: Antiangiogenic therapy combined with immunotherapy significantly improved the progression-free survival (PFS) and preliminary survival benefit for advanced clear-cell renal cell carcinoma (ccRCC). However, no combined immune therapies are currently approved for ccRCC in China. Fruquintinib (F, a highly selective VEGFR inhibitor) combined with sintilimab (S, an anti-PD-1 monoclonal antibody) showed encouraging antitumor activity in multiple solid tumors. Here, we reported the results of F plus S in metastatic ccRCC cohort from an open-label, single-arm phase 2 study (NCT03903705). Methods: Patients (pts) with pathologically confirmed metastatic ccRCC who were treatment-naive or had failed previously first-line treatment were eligible. They received F (5 mg, 2 weeks on/1 week off, orally, QD) plus S (200 mg, IV, Q3W) in 21-day cycles until disease progression or unacceptable toxicity; treatment of S was allowed for up to 24 months. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Results: As of cutoff (November 30, 2022), a total of 42 pts (22 treatment-naïve pts, and 20 previously first-line treated pts) were enrolled and received the combination treatment. Median (range) age was 59.0 (34.2-72.4) years; 34 (81.0%) pts were male. Among previously treated pts, 19 (19/20, 95.0%) pts had received VEGFR therapy as prior first-line treatment, including sunitinib (3/20, 15.0%), pazopanib (7/20, 35.0%), axitinib (2/20, 10.0%) and others (7/20, 35.0%). International Metastatic RCC Database Consortium (IMDC) risk included: favorable in 15 (35.7%) pts, intermediate in 22 (52.4%) pts, and poor in 5 (11.9%) pts. The median follow-up duration was 14.8 months (m) and 23.3 m for treatment-naive and previously treated pts, respectively. All pts had at least 1 post-baseline tumor assessment. Confirmed ORR was 68.2% and 60.0%, median duration of response was not reached (NR) and 13.9 m, and disease control rate was 95.5% and 85.0% for treatment-naive and previously treated pts, respectively. Median PFS (mPFS) was NR and 12m-PFS rate was 64.8% in treatment-naive pts; mPFS was 15.9 m in previously treated pts. The median treatment duration of F and S was both 14.7 m. All pts experienced at least 1 treatment-emergent adverse event (TEAE). Common (≥5%) grade ≥3 TEAEs were hypertension (21.4%), hypertriglyceridaemia (9.5%), amylase increased (7.1%), cerebral infarction (7.1%) and proteinuria (7.1%). No new safety signals were observed. Conclusions: F plus S demonstrated a favorable efficacy with manageable toxicity for treatment-naive and previously first-line treated metastatic ccRCC. A phase 2/3 study is being conducted to confirm this combination efficacy in the second-line treatment of ccRCC (NCT05522231). Clinical trial information: NCT03903705 .